Outline

Objective: The purpose of this study was to determine the relationship of [18F]fluoroethyl-L-tyrosine (FET) uptake in gliomas using PET and intraoperative 5-aminolevulinic acid (5-ALA) fluorescence using neuronavigated biopsies during resection as a reference. FET PET provides improved imaging of the extent of the tumor compared with MRI and 5-ALA fluorescence is used as an intraoperative marker for the identification of tumor tissue.

Methods: FET-PET was performed in 30 consecutive patients with intracerebral lesions suggestive of diffuse gliomas on MRI. Areas of FET uptake with a lesion/brain ratio >1.6 were considered as tumor positive. FET-PET data were corregistered with MRI data before surgery in order to provide optimal guidance of neuronavigated biopsies during resection. During the operation neuronavigated biopsies were taken from various FET positive areas and checked for tumor fluorescence after application of 5-aminolevulinic acid (5-ALA).In addition, a number of specimen were taken from 5-ALA positive tissue that showed no FET-uptake in PET.

Results: 13 of 30 tumors were diagnosed as low-grade gliomas (WHO grade II), 15 as anaplastic gliomas (WHO grade III) and 2 as glioblastoma multiforme. A match of FET-pos/ALA-pos biopsies was found in 76.5% (13/17) of high-grade gliomas (WHO grade III/IV) but only in 7.7% (1/13) of low grade gliomas. FET-neg/ALA-neg biopsies yielded a low-grade tumor in 53.8% (7/13) and a high-grade glioma in 11.8% (2/17). A mismatch between FET uptake and 5-ALA (FET-pos/ALA-neg) was found in 46.2% (6/13) of the low-grade and in 11.8% (2/13) of the high-grade tumors. The combination of FET-PET- and 5-ALA-positivity yielded a sensitivity for high-grade gliomas of 76.5% and a specificity of 92.3%.

Conclusions: In high-grade gliomas, increased FET-uptake is related to 5-ALA fluorescence in most cases so that FET PET may be considered as a surrogate marker for planning of 5-ALA guided tumor resection. In low-grade gliomas, however, there is a pronounced discrepancy between FET-uptake and 5-ALA fluorescence. This appears to be mainly caused by the inability of 5-ALA to accumulate in tumor areas with an intact blood-brain barrier in contrast to FET.